The synthesis of the two natural products aphidicolin and tirandamycin is proposed. The synthetic schemes are specifically designed so as to provide ready access to numerous structurally and stereochemically related derivatives which will be evaluated for their therapeutic use as anti-cancer drugs. Both molecules are known to act at the cellular level and inhibit DNA and/or RNA synthesis in bacteria and viruses. Aphidicolin, in particular, has been shown to inhibit effectively DNA synthesis in Herpes simplex virus, which is associated with the development of cancer. Tirandamycin acts as a potent inhibitor of RNA polymerase in bacterial and mammalian cell-free test systems. The mode of action of these drugs suggests that derivatives may be useful in cancer chemotherapy.